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Intravenous fluids for perioperative infusion therapy should be isotonic to maintain the body fluid homeostasis in children. Modified fluid gelatin 4% in a balanced electrolyte solution has a theoretical osmolarity of 284 mosmol LWe thus hypothesized that the infusion of gelatin would be expected to decrease plasma osmolality. We performed an in-vitro experiment and an in-vivo study to evaluate the impact of gelatin on the osmolality in children.In the in-vitro experiment, full blood samples were diluted with gelatin 4% or albumin (50 g LIn the in-vitro experiment, 65 gradually diluted blood samples from five volunteers (age 25-55 years) were analyzed. The dilution with gelatin caused no significant changes in osmolality between 0% and 100%. Compared with gelatin, the osmolality in the albumin group was significantly lower between 50% and 100% dilution (p .05). In the in-vivo study, 221 children (age 21.4 ± 30 months) were included. After gelatin infusion, the osmolality increased significantly (mean change 4.3 ± 4.8 [95% CI 3.7-4.9] mosmol kg HGelatin in a balanced electrolyte solution has isotonic characteristics in-vitro and in-vivo, despite the low theoretical osmolarity, probably caused by the (unmeasured) negative charges in the gelatin molecules contributing to the plasma osmolality. For a better evaluation of the (real) tonicity of gelatin-containing solutions, we suggest to calculate the osmolality (mosmol kg HClinicalTrials.gov (ID: NCT02495285).

In our institution, a modified WHO surgical safety checklist was implemented more than ten years ago. In retrospect, we noticed that pediatric anesthesia was underrepresented in our surgical safety checklist modification. Therefore, we added a standardized team briefing (pedSOAP-M) immediately before induction of anesthesia and hypothesized that the use of this checklist was effective to detect relevant errors with potentially harmful consequences.The primary aim was to assess the incidence and characteristics of the detected errors, and the secondary aim was to identify factors influencing error detection.This prospective observational study was performed between November 2020 and October 2021 in five operation rooms at the Children's Hospital of Hannover Medical School, Germany. The subcategories of the pedSOAP-M checklist were suction, oxygen, airway, pharmaceuticals, and monitoring. Demographic and procedure-related data and the briefing results were documented anonymously and undated, using a standardized case report form.We enrolled 1030 and analyzed 1025 patients (aged 0-18 years). Relevant errors were detected in 111 (10.8%) cases (suction 2.5%, oxygen 3.0%, airway 0.2%, pharmaceuticals 2.4%, monitoring 3.0%). In the pharmaceuticals subcategory, the most common error was entering a wrong patient weight into the perfusor syringe pumps. Experienced anesthetists detected significantly more errors than less experienced ones.The briefing tool pedSOAP-M was effective in detecting relevant errors with potentially harmful consequences. The presence of an experienced anesthetist was associated with a higher efficacy of the briefing. Particular attention should be given to entering patient weight into the anesthesia workstation and the perfusor syringe pumps.

Modified fluid gelatin 4% is approved for use in children, but there is still a surprising lack of clinical studies including large numbers of pediatric patients. Therefore, we performed a European prospective noninterventional multicenter study to evaluate the use of a modified fluid gelatin 4% in saline (sal-GEL) or an acetate-containing balanced electrolyte solution (bal-GEL) in children undergoing major pediatric surgery.The primary aim was to assess the indications and dosing of modified fluid gelatin, and the secondary aim was to assess the safety and efficacy, focusing, in particular, on routinely collected clinical parameters.Children aged up to 12 years with ASA risk scores of I-III receiving sal-GEL or bal-GEL were followed perioperatively. Demographic data, surgical procedures performed, anesthesia, hemodynamic and laboratory data, adverse events, and adverse drug reactions were documented using a standardized case report form.601 children that were investigated at 13 European pediatric centers from May 2015 to March 2020 (sal-GEL 20.1%, bal-GEL 79.9%; mean age 29.1 ± 38.6 (range 0-144) months; body weight 12.1 ± 10.5 (1.4-70) kg) were included in the analysis. The most frequent indications for GEL infusion were hemodynamic instability without bleeding (76.0%), crystalloids alone not being sufficient for hemodynamic stabilization (55.7%), replacement of preoperative deficit (26.0%), and significant bleeding (13.0%). Mean infused GEL volume was 13.0 ± 5.3 (2.4-37.5) ml kgModerate doses up to 20 ml kg

Background Neonates and infants with congenital heart disease undergoing general anesthesia have an increased risk for critical cardiovascular events. Etomidate produces very minimal changes in hemodynamic parameters in older children with congenital heart disease. There is a lack of studies evaluating the effect of etomidate on systemic and regional cerebral perfusion in neonates and infants with congenital heart disease. Aim The aim of this prospective observational study was to evaluate the effect of etomidate on systemic and regional cerebral perfusion in neonates and infants with congenital heart disease. Methods In fifty infants aged 0-11 months (24% neonates n = 12) with congenital heart disease, mean arterial blood pressure, cardiac index using electrical cardiometry, and regional cerebral oxygen saturation using near-infrared spectroscopy were measured at baseline and 1, 3, 5, and 10 minutes after induction by 0.4 mg kg-1 etomidate. Hypotension was defined as a mean arterial blood pressure under 35 mm Hg and cerebral desaturation as a regional cerebral oxygen saturation of less than 80% of baseline. Results Mean arterial blood pressure, cardiac index, and regional cerebral oxygen saturation remained stable above the predefined limits. Mean arterial blood pressure decreased slightly within a physiological range after 3 minutes (P = .005, 95% CI:-5.9 to -1.0). No significant change in cardiac index could be observed. Conclusion Etomidate 0.4mg kg-1 does not impair systemic or regional cerebral perfusion in neonates or infants with congenital heart disease.

Background The amplitude-integrated EEG (aEEG) is a widely used monitoring tool in neonatology / pediatric intensive care. It takes into account the amplitudes, but not the frequency composition, of the EEG. Advantages of the aEEG are clear criteria for interpretation and time compression. During the first year of life, the electroencephalogram (EEG) during sedation / anesthesia changes from a low-differentiated to a differentiated EEG; higher-frequency waves develop increasingly. There are few studies on the use of aEEG during pediatric anesthesia. A systematic evaluation of the aEEG in defined EEG stages during anesthesia / sedation is not yet available. Parameters of pediatric EEGs (power, median frequency, spectral edge frequency) recorded during anesthesia and of the corresponding aEEGs (upper and lower value of the aEEG trace) should be examined for age-related changes. Furthermore, it should be examined whether the aEEG can distinguish EEG stages of sedation / anesthesia in differentiated EEGs. Methods In a secondary analysis of a prospective observational study EEGs and aEEGs (1-channel recordings, electrode positions on forehead) of 50 children (age: 0–18 months) were evaluated. EEG stages: A (awake), Slow EEG, E2, F0, and F1 in low-differentiated EEGs and A (awake), B0–2, C0–2, D0–2, E0–2, F0–1 in differentiated EEGs. Results Median and spectral edge frequency increased significantly with age (p p 1 to E1 (p = 0.04, or less), and the upper and lower values of the aEEG trace increased with age (p 1 to E1 were assigned to the original EEG stage in only 19.3% of the cases. When age was added as the third variable, the rate of correct reclassifications was 28.5%. Conclusions The aEEG was not suitable for distinguishing EEG stages above the burst suppression range. For this purpose, the frequency composition of the EEG should be taken into account.

Background Infants are likely to develop anuria during laparoscopy which is uncommon in older patients. The reason for this susceptibility remains unknown. We compared the impact of CO2 pneumoperitoneum on renal perfusion and urine production in piglets compared with adolescent pigs. We furthermore investigated the effects of different resuscitation strategies. Materials and Methods Male piglets (n = 21) were divided into four groups: (a) infant controls (n = 5), (b) infants with crystalloid restitution (n = 6), (c) infants with colloidal restitution (n = 5), and (d) adolescents with crystalloid restitution (n = 5). Animals were ventilated, the central vessels and ureters were cannulated, and the animals were subjected to a 3-hour, 10 mm Hg CO2 pneumoperitoneum followed by 2-hour resuscitation. Renal perfusion was assessed by fluorescent microspheres and the rate of urine flow was measured. Results Urine production significantly decreased after insufflation only in the infant crystalloid and adolescent group, but not in controls or infants treated with colloids. In the infant crystalloid group, urine production remained at levels below 20% of baseline throughout the experiment. In this group, the renal perfusion dropped significantly after the beginning of the capnoperitoneum and remained significantly reduced throughout the experiment. Conclusion Our data indicates that capnoperitoneum impairs renal perfusion and urine production in infants. In moderate-pressure capnoperitoneum, this effect cannot be compensated by application of crystalloids but with colloids.

Purpose Ketogenic diets (KDs) are used to treat epilepsies resistant to pharmacotherapy or some inborn errors of metabolism. For prolonged anesthesia, use of balanced electrolyte solutions (BESs) supplemented with 0.5% glucose has been advocated to maintain ketosis while preventing hypoglycemia. Unfortunately, there is no BES containing 0.5% glucose available from pharmacies. In a laboratory study, we investigated the physical and chemical stability of different BES mixtures containing 0.5% glucose. Methods In total, six approaches were chosen to create a BES with 0.5% glucose: three different glucose-free BESs were supplemented with glucose. Additionally, commercially available BES containing 1% glucose was diluted with three different glucose-free BESs to obtain a solution containing 0.5% glucose. Turbidity, pH, electrical conductivity, and macroscopic appearance of these solutions were measured immediately, at 24 hours, and after 7 days, and were compared with the original BES. Results Turbidity, pH, and electrical conductivity, as well as macroscopic appearance did not exceed the changes of the controls. Conclusions No signs of incompatibility reactions could be observed in a 1-week time period. Our study supports the stability of the examined BES containing 0.5% glucose for prolonged anesthesia in patients on KD. Clinical studies are needed to evaluate if BES containing 0.5% glucose is superior in patients on KDs.

BACKGROUND While many clinics have changed their local regimen toward a more liberal policy regarding clear fluid fasting for general anesthesia, there is a lack of studies evaluating gastric emptying time in a clinical setting. AIMS Based on this and before implementation of a more liberal preoperative clear fluid fasting policy for children, we studied gastric emptying time of clear fluids in children and hypothesized that the mean gastric emptying time would be 1 hour. METHODS Between March and December 2019, children scheduled for general anesthesia at our University Children's Hospital were enrolled in this prospective observational study. After overnight fasting, gastric emptying was examined by sonographic measurements of the gastric antral area before and 5, 15, 30, 45, and 60 minutes after intake of water or fruit juice. RESULTS Twenty-six children were enrolled in this study, and 24 aged 11 (range 4-17) years were included for statistical analysis. The median ingested fluid volume was 4.7 (range 1.8-11.8) mL kg-1 . The gastric antral area of the children initially increased and subsequently decreased after intake of clear fluids and correlated significantly with fasting time (r = -0.55, P 5 mL kg-1 . There was no difference in the gastric antral area between water and fruit juice. Using a linear regression model, the calculated mean gastric emptying time of clear fluids was 52 minutes. CONCLUSION This study showed that the gastric emptying time of children after intake up to 5 mL kg-1 clear fluids was

SummaryBackground In current guidelines, 6 hours of fasting is recommended for solids to limit the risk of pulmonary aspiration during anesthesia in children. Ultrasonography has recently been introduced to evaluate gastric volumes in children in the context of preanesthetic fasting. Therefore, in this study, we firstly evaluated the precision of ultrasound assessment of gastric volume in an experimental setting and secondly studied gastric emptying times after a normal breakfast in healthy preschool children using ultrasound. Methods In a preliminary experiment, a pear-shaped elastic balloon was filled and emptied in 50 mL steps from 0 to 500 mL with water. After each step, the balloon antral area was measured using ultrasonography. Thereafter, gastric emptying was examined in healthy preschool children after normal breakfast by sonographic measurements of the gastric antral area in right lateral decubitus position at two consecutive timepoints. Correlation coefficients (Pearson, 95% CI) between the balloon antral area and the balloon volume or gastric antral area and fasting time were calculated and gastric emptying time was extrapolated by linear regression. Data are presented as mean (range). Results In the balloon experiment, the balloon volume correlated significantly with the balloon antral area (63 measurements, r=.96, P

BACKGROUND Sevoflurane induction followed by intravenous anesthesia is a widely used technique to combine the benefits of an easier and less traumatic venipuncture after sevoflurane inhalation with a recovery with less agitation, nausea, and vomiting after total intravenous anesthesia (TIVA). Combination of two different anesthetics may lead to unwanted burst suppression in the electroencephalogram (EEG) during the transition phase. OBJECTIVE The objective of this prospective clinical observational study was to identify the optimal initial propofol bolus dose for a smooth transition from sevoflurane induction to TIVA using the EEG Narcotrend Index (NI). METHODS Fifty children aged 1-8 years scheduled for elective pediatric surgery were studied. After sevoflurane induction and establishing of an intravenous access, a propofol bolus dose range 0-5 mg·kg-1 was administered at the attending anesthetist's discretion to maintain a NI between 20 and 64, and sevoflurane was stopped. Anesthesia was continued as TIVA with a propofol infusion dose of 15 mg·kg-1 ·h-1 for the first 15 min, followed by stepwise reduction according to McFarlan's pediatric infusion regime, and remifentanil 0.25 μg·kg-1 ·min-1 . Endtidal concentration of sevoflurane, NI, and hemodynamic data were recorded during the whole study period using a standardized case report form. Propofol plasma concentrations were calculated using the paedfusor dataset and a TIVA simulation program. RESULTS Median endtidal concentration of sevoflurane at the time of administration of the propofol bolus was 5.1 [IQR 4.7-5.9] Vol%. The median propofol bolus dose was 1.2 [IQR 0.9-2.5] mg·kg-1 and median NI thereafter was 33 [IQR 23-40]. Nine children presented with a NI 13-20 and three children with burst suppression in the EEG (NI 0-12); all of them received an initial propofol bolus dose >2 mg·kg-1 . Regression equation demonstrated that NI 20-64 was achieved with a 95% probability when using a propofol bolus dose of 1 mg·kg-1 after sevoflurane induction. Decrease in mean arterial blood pressure correlated significantly with propofol bolus dose (P = 0.038). After 25 min of TIVA, children younger than 2 years had a higher NI (median difference 14.0, 95%CI: 6.0-20.0, P = 0.001), higher deviations from the expected Narcotend Index (median difference 4.1, 95%CI: 3.9-4.2, P < 0.001) and lower calculated propofol plasma concentrations (median difference 0.2 μg·ml-1 , 95% CI: 0.1-0.3 μg·ml-1 , P < 0.001) than older children. CONCLUSION After sevoflurane induction, a reduced propofol bolus dose of 1 mg·kg-1 followed by TIVA according to McFarlan's regime resulted in a NI within the recommended range in children aged 1-8 years. During the course of TIVA, children younger than 2 years displayed higher NI values and more pronounced interindividual variation. Processed EEG monitoring is recommended to find adequate individual age-dependent doses.

Transpulmonary ultrasound dilution (TPUD) method, a novel indicator dilution (ID) technique for cardiac output measurement, detects and quantifies shunts, both in children and adults. However, its accuracy and reproducibility in cardiac right-to-left-shunt (RLS) detection have not been investigated. In a prospective observational study, we assessed the validity of TPUD algorithm for RLS detection in children with congenital heart disease (CHD) and proven RLS in comparison with controls without shunts between February 2010 and October 2011. As TPUD algorithm was unknown, we tested ID curve morphology, appearance time (AT) and central blood volume index (CBVI) as diagnostic criteria. TPUD identified RLS correctly in all 16 RLS subjects [median age (range): 18 months (1 month–15 years 6 months)] and excluded RLS in all 26 controls [74 months (8 months to 17 years 4 months)]. AT was significantly shorter in RLS (P

Background Due to possible serious adverse drug reactions (ADRs), the use of metamizole for postoperative pain therapy in infants is a subject of debate. Safety studies with large sample sizes are missing. Aim This prospective multicenter observational study was conducted to evaluate the use of metamizole in infants younger than 1 year undergoing surgery with a particular focus on possible serious ADRs (e.g., hemodynamic, anaphylactic or respiratory reactions, and agranulocytosis). Methods Infants aged up to 1 year (American Society of Anesthesiologists [ASA] I–III) receiving a single dose of metamizole for postoperative pain therapy were enrolled. Patient demographics, main and secondary diagnosis, surgical procedures performed, metamizole dose, hemodynamic data, use of other analgesics and regional blocks, results of pain measurement, and incidence of ADRs were documented using a standardized case report form. Results A total of 316 infants observed at five pediatric centers were included for analysis (age 4.4 ± 3.7 [0.06–12] months). Mean metamizole dose was 17.8 ± 3.1 (9.2–29.8) mg·kg−1. Mean arterial pressure (MAP) remained stable during metamizole infusion (MAP before infusion 45 ± 9.5 [25–95] and after infusion 45 ± 9.2 [25–99] mm Hg). Erythema was observed in one patient (ADRs total: 0.3%, 95% confidence interval: 0.27–0.32). No respiratory adverse events directly related to the metamizole administration and no clinical signs of agranulocytosis were reported. Conclusion Single intravenous doses of metamizole used for prevention or treatment of postoperative pain were safe in more than 300 infants younger than 1 year. The statistical probability of serious ADRs (e.g., hemodynamic, anaphylactic or respiratory reactions) was lower than 1%. The sample size and follow-up were not sufficient to detect agranulocytosis.

Summary Objectives Despite serious renal side effects in critically ill adult patients, artificial colloids are still fundamental components of perioperative fluid therapy in infants and children, although the impact of 6% hydroxyethyl starch (HES) and 4% gelatin (GEL) on renal function during pediatric surgery has not been identified yet. Aim To determine the impact of high doses of artificial colloids on renal function, we conducted an experimental animal study and hypothesized that neither the infusion of HES nor of GEL would have a serious impact on renal function. Methods Fifteen sedated piglets were randomly assigned to receive an infusion of either 50 ml·kg−1 HES or GEL, or a balanced electrolyte solution (crystalloid group). Before and 1 week after infusion, serum and urine renal function tests were recorded and renal biopsies were taken. Results Serum and urine renal function tests revealed no increase after administration of HES and GEL, and only a discrete increase in serum creatinine (median 9.8 μmol·l−1, 95% CI 4.0–19.1) in the crystalloid group. Histopathological examination indicated a sparsely, multifocal infiltration of mononuclear cells in all groups and an unspecific pyelectasia of one animal in the GEL group. Conclusions After high doses of HES or GEL in piglets, no relevant impact on renal function could be found. These results confirm that AKI after HES or GEL is very unlikely in hemodynamically stable perioperative patients with normal renal function.

Background: In older children, different electroencephalogram-based algorithms for measuring depth of anesthesia displayed a similar performance as in adults, but in infants they have not displayed the same reliability so far. According to the individual developmental state, the Narcotrend distinguishes "differentiated" electroencephalograms, which can be classified using the full Narcotrend Index scale, from "undifferentiated" electroencephalograms, which are classified using a scale with fewer stages. Objective: The objective of this prospective clinical observational study was to assess the feasibility and performance of the Narcotrend monitor in children

Summary Objectives Neonates and infants are at the highest risk of developing perioperative hypothermia. A number of methods to prevent hypothermia during pediatric anesthesia are in use, and despite the fact that conventional forced-air warmers are the most effective devices, they are not always sufficient enough to maintain body temperature. Therefore, recently a new forced-air warming system with an increased warm air flow was introduced to the market. Aim The aim of this study was to evaluate this new forced-air warming system in neonates and infants during pediatric anesthesia. We hypothesized that the new blanket alone is sufficient enough to prevent neonates and infants from intraoperative hypothermia. Methods Neonates and infants (body weight

Summary Background In pediatric anesthesia, preoperative fasting guidelines are still often exceeded. Objective The objective of this noninterventional clinical observational cohort study was to evaluate the effect of an optimized preoperative fasting management (OPT) on glucose concentration, ketone bodies, acid–base balance, and change in mean arterial blood pressure (MAP) during induction of anesthesia in children. Methods Children aged 0–36 months scheduled for elective surgery with OPT (n = 50) were compared with peers studied before optimizing preoperative fasting time (OLD) (n = 50) who were matched for weight, age, and height. Results In children with OPT (n = 50), mean fasting time (6.0 ± 1.9 h vs 8.5 ± 3.5 h, P 2 h 8% vs 70%), ketone bodies (0.2 ± 0.2 mmol·l−1 vs 0.6 ± 0.6 mmol·l−1, P < 0.001), and incidence of hypotension (MAP

Summary Background Acetate-containing balanced electrolyte solutions are frequently used for fluid therapy in pediatric anesthesia, but no studies investigating the compatibility with common anesthetic drugs are available. Aim To reveal possible incompatibilities between common anesthetic drugs and the acetate-containing balanced electrolyte solutions BS (Sterofundin ISO; B.Braun Melsungen AG, Melsungen, Germany) and BS-G1 (E148G1 Pad; Serumwerk Bernburg AG, Bernburg, Germany), with normal saline (NS) as control. Methods All tested infusion solutions were mixed 1 : 1 with 28 common anesthetic drugs in concentrations used in daily clinical practice. Electrical conductivity, pH, and turbidimetric light diffusion at 405 nm were measured. Macroscopic changes such as gross precipitation, change in color, or bubble formation were also assessed. All measurements were performed immediately after mixing as well as 30 and 60 min after. Results The vast majority of drugs showed no significant change in pH, electric conductivity, turbidimetric detectable light diffusion, or macroscopic appearance after mixing with BS, BS-G1, and NS. Phenytoin immediately precipitated in response to all tested solutions as did diazepam. Thiopental precipitated after mixing with BS only. Conclusions Most of the tested drugs did not show any signs or evidence of incompatibility reactions. However, phenytoin and diazepam should not be in contact with the three tested solutions, including NS. Thiopental should be used with caution because it can precipitate in solutions with a low pH (e.g., BS).

Summary Objective: This prospective clinical observational study was conducted to investigate the effects of contrast medium on acid–base balance, electrolyte concentrations, and osmolality in children. Background: For pediatric cardiac catheterization, high doses of nonionic hyperosmolar contrast medium are widely used. Methods: Forty pediatric patients (age 0–16 years) undergoing cardiac angiography with more than 3 ml·kg−1 of nonionic hyperosmolar contrast medium (Iomeprol) were enrolled, and the total amount of the contrast agent given was documented. Before and after contrast medium administration, a blood sample was collected to analyze electrolytes, acid–base parameters, osmolality, hemoglobin, and hematocrit. Results: After cardiac catheterization, pH, hemoglobin, hematocrit, bicarbonate, base excess, sodium, chloride, calcium, anion gap and strong ion difference decreased, whereas osmolality increased significantly (base excess −1.8 ± 1.8 vs −3.4 ± 2.3, sodium 138 ± 2.9 vs 132 ± 4.1 mm, osmolality 284 ± 5.7 vs 294 ± 7.6 mosmol·kg−1, P

Summary Background: Neonates have a higher metabolic rate and an increased risk of perioperative hypoglycemia and lipolysis, but during anesthesia, both oxygen consumption and metabolic rate are decreased, and this may lead to reduced intraoperative glucose requirements. Objective: The objective of this prospective multicentre observational postauthorisation safety study was to evaluate the intraoperative use of a novel isotonic balanced electrolyte solution with a low glucose concentration of 1% (BS-G1) in neonates with a particular focus on changes in acid-base, electrolyte, and glucose concentrations. Methods: Following the local ethics committee approval, neonates with a postmenstrual age under 45 weeks and an ASA risk score of I–IV undergoing intraoperative administration of BS-G1 were enrolled. Patient demographics, the performed procedure, adverse drug reactions, hemodynamic data, and the results of blood gas analysis before and after infusion were documented with a focus on changes in acid-base, electrolyte, and glucose concentrations. Results: In 66 neonates (ASA I–IV; postmenstrual age 38 ± 4, range 25–45 weeks; body weight 2.9 ± 0.9, range 0.65–4.6 kg), the mean infusion rate was 10.4 ± 3.2 (range 4.5–19.6) ml·kg−1·h−1 BS-G1. During the infusion, hemoglobin, hematocrit, bicarbonate, base excess, anion gap, strong ion difference, and calcium decreased, and chloride and glucose increased significantly within the physiological range. All other measured parameters including sodium and lactate remained stable. Neither hypoglycemia (glucose 10 mm) was documented after BS-G1 infusion. No adverse drug reactions were reported. Conclusion: The study shows that the intraoperative use of an isotonic balanced electrolyte solution with 1% glucose and a mean infusion rate of 10 ml·kg−1·h−1 helps to avoid acid-base dysbalance, hyponatraemia, hypoglycemia, ketoacidosis, and hyperglycemia in surgical neonates. A careful intraoperative monitoring and adaptation of the infusion rate as needed is crucial because the glucose and fluid requirements may vary widely between subjects.